This project addresses issues relevant to the CNS mechanisms of pain perception in terms of 1) gender differences in healthy individuals, and 2) contributing factors for temporomandibular disorder (TMD) pain. Two CNS mechanisms that influence nociceptive processing and resulting pain -- temporal summation (-I-S) of pain and diffuse noxious inhibitory control (DNIC) - will be evaluated in a series of human psychophysical experiments. TS is the increase in perceived pain intensity when noxious stimuli of a constant intensity are delivered at a sufficiently rapid frequency. TS is centrally mediated and reflects transient up-regulation of the dorsal horn nociceptive neurons' excitability in the spinal cord, and potentially higher CNS regions. One study has reported that TS of heat pain is greater in females than in males, suggesting that females may have more hyperexcitable central nociceptive neurons. Similarly, TMD patients have been reported to show higher temporal summation of heat pain than healthy controls, indicating that up-regulated central processing of nociceptive input may constitute an underlying pathophysiological basis of TMD. One purpose of this project is to investigate differences in temporal summation of mechanically evoked pain between healthy females and healthy males, as well as between TMD patients and healthy controls. Both the sensory and the affective dimensions of pain, as well as the frequency-dependent profile of temporal summation of pain will be evaluated. Moreover, it will be determined if there is a significant correlation between temporal summation of pain and measures of clinical pain in TMD patients. DNIC is the phenomenon in which persistent noxious stimulation evokes an endogenous analgesic system, resulting in a global attenuation of nociceptive signals. Accordingly, subsequent noxious stimulation elsewhere on the body produces less pain than it otherwise would. Several studies indicate that DNIC engages the endogenous opiate system. Given gender differences in the efficacy of exogenous opiates, this project will examine whether DNIC is significantly stronger in men than women. Additionally, endogenous analgesic systems may be attenuated in cases of prolonged pain, thus contributing to the difficulty in managing chronic pain. This project will compare DNIC efficacy in TMD pain patients, and a sex- and age-matched healthy control group, to determine whether there is a significant difference in the evocation of the endogenous analgesic system. Identifying the roles of these two specific nociceptive processing mechanisms in TMD pain would provide focus for the development of appropriately targeted pain relief treatments. Identifying gender differences in these two nociceptive processing mechanisms could explain, in part, the female prevalence of TMD, and possibly other chronic pain conditions. In addition, establishing such gender differences would highlight the need consider the person's sex in addressing pain treatment in general.